In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritig...In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.展开更多
G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways...G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.展开更多
Filamentous fungi employ conserved eukaryotic signaling pathway to detect and respond to environmental signals, including the presence of the host. Genetic experiment in which a particular signaling protein is lost, o...Filamentous fungi employ conserved eukaryotic signaling pathway to detect and respond to environmental signals, including the presence of the host. Genetic experiment in which a particular signaling protein is lost, or its activity enhanced, have defined some of the function of heterotrimeric G proteins and MAP kinases in development and virulence. A hallmark of these studies is that orthologs in different species may have different functions. Antagonistic fungal-fungal interactions form the basis for biological control of plant disease. These interactions may employ novel modes of regulation by conserved signaling elements. Tag1, a G protein α subunit of Trichoderma. atroviride belonging to fungal Gi class, is involved in repression of sporulation and hyphal coiling(1). Deletion of ortholog of this gene, TgaA, in Trichoderma (Gliocladium) virens, however, did not affect sporulation and growth, yet tgaA mutants are unable to parasitize S. rolfsii sclerotia(2). Mutation of a second G α subunit gene is now under study. TmkA, a MAPK gene of T. virens, is involved in biocontrol properties and repression of conidiation(3). Using suppression-subtraction hybridization and other approaches, we are beginning to identify additional elements of the signaling cascades and their downsteam targets. The role of G protein and MAPK genes are sometimes specific to a particular host fungus or to parasitism of mycelia or sclerotia(2,3). Also of relevance to biocontrol, signal transduction pathway provide a means to alter the balance between sporulation, mycelial growth and hyphal coiling.展开更多
Mycoparasitic species of Trichoderma are commercially applied as biological control agents against various fungal pathogens. The mycoparasitic interaction is host specific and includes recognition, attack and subseque...Mycoparasitic species of Trichoderma are commercially applied as biological control agents against various fungal pathogens. The mycoparasitic interaction is host specific and includes recognition, attack and subsequent penetration and killing of the host. Investigations on the underlying events revealed that Trichoderma responds to multiple signals from the host (e.g. lectins or other ligands such as low molecular weight components released from the host’s cell wall) and host attack is accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Degradation of the cell wall of the host fungus is-besides glucanases and proteases-mainly achieved by chitinases. In vivo studies showed that the ech42 gene (encoding endochitinase 42) is expressed before physical contact of Trichoderma with its host, probably representing one of the earliest events in mycoparasitism, whereas Nag1 (N-acetylglucosaminidase) plays a key role in the general induction of the chitinolytic enzyme system of T. atroviride . Investigations on the responsible signal transduction pathways of T. atroviride led to the isolation of several genes encoding key components of the cAMP and MAP kinase signaling pathways, as alpha and β subunits of heterotrimeric G proteins, the regulatory subunit of cAMP-dependent protein kinase, adenylate cyclase, and three MAP kinases. Analysis of knockout mutants, generated by Agrobacterium-mediated transformation, revealed that at least two alpha-subunits of heterotrimeric G proteins are participating in mycoparasitism-related signal transduction. The Tga1 G alpha subunit was shown to be involved in mycoparasitism-related processes such as chitinase expression and overproduction of toxic secondary metabolites, whereas Tga3 was found to be completely avirulent showing defects in chitinase formation and host recognition.展开更多
The study was conducted to investigate the effect and mechanism of dietary quercetin supplementation on protein utilization of Arbor Acres(AA)broilers.A total of 2401-day-old AA broilers were randomly allocated to fou...The study was conducted to investigate the effect and mechanism of dietary quercetin supplementation on protein utilization of Arbor Acres(AA)broilers.A total of 2401-day-old AA broilers were randomly allocated to four treatments with six replicates,comprising 10 broilers each replicate(60 broilers per treatment).Birds were fed either a corn-soybean meal basal diet without quercetin(control)or a basal diet supplemented with 0.2,0.4 or 0.6 g of quercetin per kg feed,and the trial lasted 42 days.Dietary quercetin supplementation tended to increase the apparent metabolic rate of protein(p=0.076)and the content of serum albumin(p=0.062)in AA broilers.Compared with the control,dietary quercetin supplementation increased the contents of protein in breast muscle(p<0.05)and in thigh muscle(p=0.053).In addition,quercetin up-regulated mRNA expression of insulin-like growth factor 1(IGF-1),phosphatidylinositol 3-kinase(PI3K),target of rapamycin(TOR),ribosomal protein S6 kinase 1(S6K1),eukaryotic translation initiation factor 4E(eIF4E),eukaryotic translation initiation factor 4G(eIF4G),eukaryotic elongation factor 2(eEF2)and eukaryotic translation initiation factor 4B(eIF4B)genes and down-regulated mRNA expression of eukaryotic elongation factor 2 kinase(eEF2K)and eukaryotic initiation factor 4E binding protein1(4E-BP1)genes in breast muscle,thigh muscle and liver of AA broilers(p<0.05).The present results suggested that dietary quercetin supplementation enhanced protein utilization in broilers by activating TOR signaling pathway.展开更多
文摘In order to clarify the mechanism of action of licorice flavonoids in alleviating bone loss caused by osteoporosis,this study compared the effects of four glycyrrhiza flavonoids,naringenin,liquiritigenin,isoliquiritigenin,and licochalcone A,on osteogenic differentiation and mineralization by molecular docking simulation,alkaline phosphatase(ALP)activity and osteocalcin(OCN)content assays,and Runt-related transcription factor 2(Runx2)expression,and explored their potential molecular mechanisms.The results of molecular docking showed that the docking score of liquiritigenin with the estrogen receptor(ER)was the highest.All four flavonoids up-regulated ALP activity and OCN concentration in MC3T3-E1 cells,thereby elevating the mineralization level,among which liquiritigenin was the most effective.Moreover,treatment with a phosphatidylinositol-3-kinase(PI3K)inhibitor(LY294002)inhibited liquiritigenin from inducing increased phosphorylation levels in the PI3K/protein kinase B(AKT)signaling pathway and up-regulation of Runx2 expression,suggesting that PI3K and AKT were involved in osteogenic action.Liquiritigenin reversed bone mineral density loss in a zebrafish osteoporosis model.These findings suggest that liquiritigenin has the most significant osteogenic effect among the four estrogen-like flavonoids,stimulating osteoblast differentiation and bone mineralization through the activation of Runx2 via the PI3K/AKT signaling pathways.In conclusion,this study highlights the great potential of liquiritigenin for preventing and treating osteoporosis.
基金supported by National Natural Science Foundation of China(81330081,81473223and 81673444)Anhui Province Postdoctoral Science Foundation(2016B134)
文摘G protein coupled receptors(GPCRs)are transmembrane receptor proteins,which allow signals to transfer across membrane.GPCRs include a large number of receptors,different receptors mediated different signaling pathways of GPCRs-adenylyl cyclase(AC)-cyclic adenosine 3',5'-monophosphate(c AMP),including β2 adrenergic receptors(β2-ARs)-AC-c AMP signaling pathways,E-prostanoid2/4(EP2/4)-AC-cA MP signaling pathways.Regulatory proteins,such as G protein coupled receptor kinases(GRKs)andβ-arrestins,play important modulatory roles in GPCRs signaling pathway.GPCRs signaling pathway and regulatory proteins implicate the pathogenesis process of inflammatory and immune response.Rheumatoid arthritis(RA)is an autoimmune disease characterized by synovitis and accompanied with inflammatory and abnormal immune response.This article review the advances on GPCRs signaling pathway implicating in the inflammatory and immune response of RA.
文摘Filamentous fungi employ conserved eukaryotic signaling pathway to detect and respond to environmental signals, including the presence of the host. Genetic experiment in which a particular signaling protein is lost, or its activity enhanced, have defined some of the function of heterotrimeric G proteins and MAP kinases in development and virulence. A hallmark of these studies is that orthologs in different species may have different functions. Antagonistic fungal-fungal interactions form the basis for biological control of plant disease. These interactions may employ novel modes of regulation by conserved signaling elements. Tag1, a G protein α subunit of Trichoderma. atroviride belonging to fungal Gi class, is involved in repression of sporulation and hyphal coiling(1). Deletion of ortholog of this gene, TgaA, in Trichoderma (Gliocladium) virens, however, did not affect sporulation and growth, yet tgaA mutants are unable to parasitize S. rolfsii sclerotia(2). Mutation of a second G α subunit gene is now under study. TmkA, a MAPK gene of T. virens, is involved in biocontrol properties and repression of conidiation(3). Using suppression-subtraction hybridization and other approaches, we are beginning to identify additional elements of the signaling cascades and their downsteam targets. The role of G protein and MAPK genes are sometimes specific to a particular host fungus or to parasitism of mycelia or sclerotia(2,3). Also of relevance to biocontrol, signal transduction pathway provide a means to alter the balance between sporulation, mycelial growth and hyphal coiling.
文摘Mycoparasitic species of Trichoderma are commercially applied as biological control agents against various fungal pathogens. The mycoparasitic interaction is host specific and includes recognition, attack and subsequent penetration and killing of the host. Investigations on the underlying events revealed that Trichoderma responds to multiple signals from the host (e.g. lectins or other ligands such as low molecular weight components released from the host’s cell wall) and host attack is accompanied by morphological changes and the secretion of hydrolytic enzymes and antibiotics. Degradation of the cell wall of the host fungus is-besides glucanases and proteases-mainly achieved by chitinases. In vivo studies showed that the ech42 gene (encoding endochitinase 42) is expressed before physical contact of Trichoderma with its host, probably representing one of the earliest events in mycoparasitism, whereas Nag1 (N-acetylglucosaminidase) plays a key role in the general induction of the chitinolytic enzyme system of T. atroviride . Investigations on the responsible signal transduction pathways of T. atroviride led to the isolation of several genes encoding key components of the cAMP and MAP kinase signaling pathways, as alpha and β subunits of heterotrimeric G proteins, the regulatory subunit of cAMP-dependent protein kinase, adenylate cyclase, and three MAP kinases. Analysis of knockout mutants, generated by Agrobacterium-mediated transformation, revealed that at least two alpha-subunits of heterotrimeric G proteins are participating in mycoparasitism-related signal transduction. The Tga1 G alpha subunit was shown to be involved in mycoparasitism-related processes such as chitinase expression and overproduction of toxic secondary metabolites, whereas Tga3 was found to be completely avirulent showing defects in chitinase formation and host recognition.
基金Supported by the National Natural Science Foundation of China(31872377)。
文摘The study was conducted to investigate the effect and mechanism of dietary quercetin supplementation on protein utilization of Arbor Acres(AA)broilers.A total of 2401-day-old AA broilers were randomly allocated to four treatments with six replicates,comprising 10 broilers each replicate(60 broilers per treatment).Birds were fed either a corn-soybean meal basal diet without quercetin(control)or a basal diet supplemented with 0.2,0.4 or 0.6 g of quercetin per kg feed,and the trial lasted 42 days.Dietary quercetin supplementation tended to increase the apparent metabolic rate of protein(p=0.076)and the content of serum albumin(p=0.062)in AA broilers.Compared with the control,dietary quercetin supplementation increased the contents of protein in breast muscle(p<0.05)and in thigh muscle(p=0.053).In addition,quercetin up-regulated mRNA expression of insulin-like growth factor 1(IGF-1),phosphatidylinositol 3-kinase(PI3K),target of rapamycin(TOR),ribosomal protein S6 kinase 1(S6K1),eukaryotic translation initiation factor 4E(eIF4E),eukaryotic translation initiation factor 4G(eIF4G),eukaryotic elongation factor 2(eEF2)and eukaryotic translation initiation factor 4B(eIF4B)genes and down-regulated mRNA expression of eukaryotic elongation factor 2 kinase(eEF2K)and eukaryotic initiation factor 4E binding protein1(4E-BP1)genes in breast muscle,thigh muscle and liver of AA broilers(p<0.05).The present results suggested that dietary quercetin supplementation enhanced protein utilization in broilers by activating TOR signaling pathway.
